Nutritional status in oncological patients may differ according to several modifiable and non-modifiable factors. Knowledge of the epidemiology of malnutrition/cachexia/sarcopenia may help to manage these complications early in the course of treatment, potentially impacting patient quality of life, treatment intensity, and disease outcome. Therefore, this narrative review aimed to critically evaluate the current evidence on the combined impact of tumor- and treatment-related factors on nutritional status and to draw some practical conclusions to support the multidisciplinary management of malnutrition in cancer patients. A comprehensive literature search was performed from January 2010 to December 2020 using different combinations of pertinent keywords and a critical evaluation of retrieved literature papers was conducted. The results show that the prevalence of weight loss and associated symptoms is quite heterogeneous and needs to be assessed with recognized criteria, thus allowing a clear classification and standardization of therapeutic interventions. There is a large range of variability influenced by age and social factors, comorbidities, and setting of cures (community-dwelling versus hospitalized patients). Tumor subsite is one of the major determinants of malnutrition, with pancreatic, esophageal, and other gastroenteric cancers, head and neck, and lung cancers having the highest prevalence. The advanced stage is also linked to a higher risk of developing malnutrition, as an expression of the relationship between tumor burden, inflammatory status, reduced caloric intake, and malabsorption. Finally, treatment type influences the risk of nutritional issues, both for locoregional approaches (surgery and radiotherapy) and for systemic treatment. Interestingly, personalized approaches based on the selection of the most predictive malnutrition definitions for postoperative complications according to cancer type and knowledge of specific nutritional problems associated with some new agents may positively impact disease course. Sharing common knowledge between oncologists and nutritionists may help to better address and treat malnutrition in this population.

Ghrelin is a gastric hormone increased during caloric restriction and fat depletion. A role of ghrelin in the regulation of lipid and energy metabolism is suggested by fat gain independent of changes in food intake during exogenous ghrelin administration in rodents. We investigated the potential effects of peripheral ghrelin administration (two times daily 200-ng sc injection for 4 days) on triglyceride content and mitochondrial and lipid metabolism gene expression in rat liver and muscles. Compared with vehicle, ghrelin increased body weight but not food intake and circulating insulin. In liver, ghrelin induced a lipogenic and glucogenic pattern of gene expression and increased triglyceride content while reducing activated (phosphorylated) stimulator of fatty acid oxidation, AMP-activated protein kinase (AMPK, all P < 0.05), with unchanged mitochondrial oxidative enzyme activities. In contrast, triglyceride content was reduced ( P < 0.05) after ghrelin administration in mixed (gastrocnemius) and unchanged in oxidative (soleus) muscle. In mixed muscle, ghrelin increased ( P < 0.05) mitochondrial oxidative enzyme activities independent of changes in expression of fat metabolism genes and phosphorylated AMPK. Expression of peroxisome proliferator-activated receptor-γ, the activation of which reduces muscle fat content, was selectively increased in mixed muscle where it paralleled changes in oxidative capacities ( P < 0.05). Thus ghrelin induces tissue-specific changes in mitochondrial and lipid metabolism gene expression and favors triglyceride deposition in liver over skeletal muscle. These novel effects of ghrelin in the regulation of lean tissue fat distribution and metabolism could contribute to metabolic adaptation to caloric restriction and loss of body fat.

Context: Metabolic syndrome shows clustered metabolic abnormalities with major roles for insulin resistance and obesity. Ghrelin is a gastric hormone whose total plasma concentration (T-Ghr) is associated positively with insulin sensitivity and is reduced in obesity. Ghrelin circulates in acylated (A-Ghr) and desacylated (D-Ghr) forms, but their potential differential associations with insulin resistance and whether they are differentially altered in obesity remain undefined. Objective: Our objective was to determine potential differential associations of ghrelin forms with insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and the impact of obesity on their plasma concentrations in metabolic syndrome. Design: This is a cross-sectional study. Setting: The study was performed in a metabolic outpatient unit. Patients: Patients with metabolic syndrome (National Cholesterol Education Program-Adult Treatment Panel III; n = 45, 23 males/22 females) were included in the study. Main Outcomes: The main study outcomes were metabolic syndrome criteria, HOMA-IR, and ghrelin forms. Results: Plasma insulin and HOMA-IR were associated negatively with T-Ghr and D-Ghr but positively with A-Ghr and acylated to desacylated ghrelin (A/D-Ghr) ratio (n = 45; P < 0.05). Compared with nonobese [body mass index (BMI) < 27.5 kg/m²; n = 12, six males/six females], obese metabolic syndrome patients (BMI > 27.5 kg/m²; n = 33) had lower T-Ghr and D-Ghr but comparable A-Ghr and higher A/D-Ghr ratio (P < 0.05). BMI and waist circumference (WC) were positively related with HOMA-IR (n = 45; P < 0.05). However, opposite associations between A/D-Ghr ratio and HOMA-IR remained significant after adjustment for sex and BMI (or WC). Additional obese individuals without metabolic syndrome (n = 10: age-, sex-, BMI-, and WC-matched to obese metabolic syndrome patients) had lower T-Ghr but higher A-Ghr (P < 0.05) compared with age-, sex-matched healthy nonobese counterparts (n = 15). T-Ghr and A-Ghr were comparable in obese with or without metabolic syndrome. Conclusion: Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.

Background: Muscle inactivity and low energy intake commonly occur in persons with acute or chronic disease, in astronauts during space flight, and during aging. Objective: We used a crossover design to investigate the effects of the interactions of inactivity and calorie restriction on whole-body composition and protein kinetic regulation in 9 healthy volunteers. Design: Lean body mass (LBM) was measured by using dual-energy X-ray absorptionmetry before and at the end of 14-d periods of bed rest (B) and controlled ambulation (A) in patients receiving eucaloric (E) or hypocaloric (H) (≈80% of total energy expenditure) diets. Whole-body leucine kinetics were determined at the end of the 4 study periods by using a standard stable-isotope technique in the postabsorptive state and during a 3-h infusion of a 0.13 g · kg LBM⁻¹ · h⁻¹ amino acid mixture. Results: In the postabsorptive state, we found a significant (P = 0.04) bed rest × hypocaloric diet interaction for the rate of leucine oxidation, an index of net protein catabolism (A+E: 0.23 ± 0.01; B+E: 25 ± 0.01; A+H: 0.23 ± 0.01; B+H: 0.28 ± 0.01 μmol · min⁻¹ · kg LBM⁻¹). Bed rest significantly (P < 0.01) decreased amino acid–mediated stimulation of nonoxidative leucine disappearance, an index of protein synthesis (A+E: 35 ± 2%; B+E: 30 ± 2%; A+H: 41 ± 3%; B+H: 32 ± 2%). B+H decreased LBM by 1.10 ± 0.1 kg, which is significantly (P < 0.01) greater than the decrease seen with A+E, A+H, or B+E. Conclusion: Calorie restriction enhanced the catabolic response to inactivity by combining greater protein catabolism in the postabsorptive state with an impaired postprandial anabolic utilization of free amino acids.

Diminished muscular activity is associated with alterations of protein metabolism. The aim of this study was to evaluate the effect of short‐term muscle inactivity on regulation of whole‐body protein deposition during amino acid infusion to simulate an experimental postprandial state. We studied nine healthy young volunteers at the end of 14 day periods of strict bed rest and of controlled ambulation using a cross‐over design. Subjects received a weight‐maintaining diet containing 1 g protein kg⁻¹ day⁻¹. l[1‐¹³C]leucine was used as a marker of whole‐body protein kinetics in the postabsorptive state and during a 3 h infusion of an amino acid mixture (0.13 g amino acid (kg lean body mass)⁻¹ h⁻¹). In the postabsorptive state, bed rest decreased (P < 0.05) the rate of leucine disposal (R_d) to protein synthesis and tended to decrease leucine rate of appearance (R_a) from proteolysis, whereas the rate of leucine oxidation did not change significantly. Amino acid infusion increased leucine R_d to protein synthesis and oxidation and decreased leucine R_a from proteolysis in both the bed rest and ambulatory conditions. Changes from basal in leucine R_d to protein synthesis were lower (P < 0.05) during bed rest than those in the ambulatory period, whereas changes in leucine R_a from proteolysis and oxidation were not significantly different. During amino acid infusion, net leucine deposition into body protein was 8 ± 3% lower during bed rest than during the ambulatory phase. In conclusion, short‐term bed rest leads to reduced stimulation of whole‐body protein synthesis by amino acid administration. Results of this study were, in part, presented at the meeting, Experimental Biology, 2004, Washington DC.